PROMETHAZINE-INDUCED THROMBOPHLEBITIS IN A NIGERIAN MAN: A CASE REPORT.

Introduction: Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness, allergic conditions, nausea and vomiting, in addition to its use as a sedative. Promethazine has vesicant properties and is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration may result in thrombophlebitis, unintentional intra-arterial administration, perivascular extravasation and tissue necrosis. To the best of our knowledge there is no previous published report of promethazine-induced thrombophlebitis from sub- Saharan Africa. Case Report: A 29-year-old Nigerian male was admitted at our hospital on account of malaria with acute gastroenteritis. Due to persistent vomiting, he was administered 25 mg of promethazine injection via a size 22G intravenous cannula which was inserted the previous day on the anteromedial aspect of his right forearm and maintained with continuous intravenous crystalloid infusion. Upon administration of promethazine, he experienced intense burning and erythema. The cannula was removed immediately, another cannula was inserted on the contralateral arm, and promethazine was replaced with ondansetron. Subsequently, he developed a tender, subcutaneous cord-like swelling extending from the middle-third of the anteromedial aspect of his right forearm, corresponding with the site of previous venous cannulation. Ultrasonography revealed a hypoechoic, non-compressible basilic vein, with no flow on colour Doppler interrogation, in keeping with superficial thrombophlebitis. He was treated with a topical anti-inflammatory agent, and the pain and redness subsided after four weeks. Conclusion: The preferred parenteral route of administration of promethazine is deep intramuscular injection. Recommendations to prevent promethazine-induced thrombophlebitis include: use of large and patent veins, use of lower doses, drug dilution and slow administration, use of alternative therapies, and patient education. Promethazine-induced tissue injury is under-reported in this part of the world. Creating awareness through this case report would help reduce the morbidity following promethazine administration.

A study for the evaluation of safety and tolerability of intravenous high-dose iron sucrose in patients with iron deficiency anemia due to gastrointestinal bleeding.

INTRODUCTION: The provision of adequate iron to support erythropoiesis in iron deficient patients is a time-consuming process which may present compliance problems for patients in the outpatient setting. The aim of the present study was to evaluate the safety and tolerability of intravenous high-dose iron sucrose therapy specifically in patients with iron deficiency anemia (IDA) due to gastrointestinal blood loss. METHODS: A single dose of iron sucrose of 7 mg iron/kg body weight (not exceeding 500 mg) was infused over 3.5 hours in 31 consecutive patients with IDA due to gastrointestinal blood loss. Safety and tolerability of the therapy was assessed by the occurrence of adverse events under therapy and up to one week after completion of the study. Further examinations comprised vital parameters, ECG, and clinical chemistry including iron indices. RESULTS: A total of 14 adverse events were observed in 10 patients, of which two adverse events in two patients were considered as being definitely related to drug administration. None of the patients had to be withdrawn from therapy. Significant changes in vital parameters and ECG during therapy and follow-up were not observed and clinical chemistry remained unchanged. DISCUSSION: A single intravenous high-dose iron sucrose therapy in patients with IDA due to gastrointestinal blood loss appears to be safe and therefore is a therapeutic option which may save time and improve patient compliance.

Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil.

We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg-1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan. Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced.

[Case report of acute intoxication from intravenous injection of petroleum] . / A propos d'un cas d'intoxication aiguë par injection intraveineuse directe de pétrole.

A 18-year-old patient injected intravenously 2.5 mL of paraffin oil into the right upper limb. It caused a local thrombophlebitis with a slow evolution. A collapsus occurred on the sixth day. The authors obtained a clinical recovery of the limb after heparine and oral anticoagulation.

Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer.

BACKGROUND: Herbal mixtures are popular alternatives to demonstrated therapies. PC-SPES, a commercially available combination of eight herbs, is used as a nonestrogenic treatment for cancer of the prostate. Since other herbal medicines have estrogenic effects in vitro, we tested the estrogenic activity of PC-SPES in yeast and mice and in men with prostate cancer. METHODS: We measured the estrogenic activity of PC-SPES with transcriptional-activation assays in yeast and a biologic assay in mice. We assessed the clinical activity of PC-SPES in eight patients with hormone-sensitive prostate cancer by measuring serum prostate-specific antigen and testosterone concentrations during and after treatment. RESULTS: In complementary yeast assays, a 1:200 dilution of an ethanol extract of PC-SPES had estrogenic activity similar to that of 1 nM estradiol, and in ovariectomized CD-1 mice, the herbal mixture increased uterine weights substantially. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations (P<0.05), and in eight of eight patients it decreased serum concentrations of prostate-specific antigen. All eight patients had breast tenderness and loss of libido, and one had venous thrombosis. High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol. CONCLUSIONS: PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects.

Skin necrosis and venous thrombosis from subcutaneous injection of charcoal lighter fluid (naptha).

A 33-year-old white man injected approximately 4 cc of charcoal lighter fluid (99.4% naptha/0.6% inert ingredients) subcutaneously into his left antecubital fossa. The injection resulted in the toxic necrosis of his volar forearm skin extending proximally to mid-humerus and distally to the metacarpophalangeal joints of the left hand dorsally over a 6-day period. The patient ultimately required extensive surgical debridement, secondary operative closure, and approximately 150 cm2 of split-thickness skin grafting. This case demonstrates the potential for widespread, delayed toxic necrosis of the skin resulting from subcutaneous injection of naptha. This patient's case appears to represent the most severe and widespread case of toxic necrosis of the skin resulting from the subcutaneous injection of hydrocarbons reported in the literature. This case also demonstrates extensive toxic thrombophlebitis not reported in prior cases involving subcutaneous injection of hydrocarbons.

Protein S and protein C level changes with adjuvant tamoxifen therapy in postmenopausal women.

Tamoxifen citrate is a synthetic antiestrogen that provides survival benefit when given as adjuvant treatment in postmenopausal women with breast cancer. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible procoagulant effects associated with tamoxifen therapy we evaluated changes in protein S and C activity levels in 58 postmenopausal women with surgically resected breast cancer who were disease-free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. The changes in protein C activities for the tamoxifen group (mean level = 113%) compared to those in the placebo group (mean level = 115%) were not significant (p = 0.45). Protein S activity levels increased while protein C activity levels decreased from baseline at 24 months in both tamoxifen and placebo groups. We conclude that the possible thrombophlebitis-promoting effect of tamoxifen in postmenopausal women is unlikely to be explained on the basis of protein S and protein C activity level changes.

Anticoagulant therapy for prevention of spontaneous abortion in a patient with a lupus anticoagulant.

Lupus anticoagulants are associated with venous and arterial thrombosis and with recurrent spontaneous abortion resulting from placental infarction. Treatment with high-dose prednisone and aspirin has been reported to reduce the otherwise very high frequency of spontaneous abortion in affected women. We report the case of a young woman with an idiopathic lupus anticoagulant who had a history of arterial and venous thrombosis and of previous spontaneous abortion; anticoagulation throughout pregnancy was associated with normal fetal growth and with an absence of placental infarction. We conclude that anticoagulation without concurrent prednisone or aspirin may provide an alternative approach to prevention of habitual abortion in some women with lupus anticoagulants.

[Recurring thrombosis of the subclavian vein during estrogen therapy of prostatic cancer]. / Rezidivierende Thrombose der Vena subclavia während Ostrogentherapie eines Prostatakarzinoms.

A cardiac pacemaker had been implanted in a patient with carcinoma of the prostate because of a sick sinus node. Thrombosis of the left subclavian vein occurred four weeks later. After complete recanalisation following thrombolytic treatment a recurrence of the thrombosis occurred during high-dosage intravenous oestrogen treatment. Continuous increase of prothrombin time was observed during oestrogen administration while the oral anticoagulation had remained unaltered. This indicated increase of synthesis of vitamin-K-dependent clotting factors by the oestrogens. This case demonstrates that in patients with implanted material and oral long-term anticoagulation the indication for oestrogen treatment must be extremely accurately. In every case very close surveillance of coagulation is necessary.

Treatment of serious obstetric and gynecologic infections with cefoxitin.

In order to evaluate the efficacy of cefoxitin, 25 patients with serious pelvic infections admitted to a community hospital were treated with the drug. Twenty-one patients (84%) responded to this therapy. Three of the four failures (75%) had a pelvic abscess. Resistant organisms included Staphylococcus aureus, Pseudomonas aeruginosa and enterococci. The adverse reactions encountered were due to localized phlebitis, which occurred in three patients (12%). The study demonstrated that cefoxitin was successful as a single agent in the treatment of serious soft-tissue pelvic infections.

Effects of large doses of phenylbutazone administration to horses.

The effects of large doses of phenylbutazone were evaluated in clinically normal horses. The drug was given to 4 groups of 2 horses each at the rate of 30 mg/kg of body weight, orally, or 30, 15, or 8 mg/kg IV daily for up to 2 weeks. All horses became anorectic and depressed after 2 to 4 phenylbutazone treatments, and the horses given 15 or 30 mg/kg died on or between days 4 and 7 of treatment. A decrease in total blood neutrophil count occurred in all horses, and was associated with toxic left shift in horses given the 2 larger dosage schedules. The horses also had progressive increases in serum urea nitrogen, creatinine, and phosphorus concentrations, accompanied by decreasing serum calcium concentrations. There was a progressive decrease in total serum protein in all 8 horses. Gastrointestinal ulcerations, renal papillary necrosis, and vascular thromboses were the predominant postmortem findings.

Local reactions to i.v. diazepam in three different formulations.

Local venous reactions during and after i.v injections of three different formulations of diazepam were studied in 200 patients undergoing gastroscopy. Of the patients receiving diazepam in propylene glycol (Stesolid) 78% experienced pain on injection and 48% subsequently developed clinical evidence of thrombophlebitis. The figures for Stesolid MR (diazepam in Cremophor EL) were 38% and 9% respectively. A significant decrease was achieved (pain on injection 1%; clinical thrombophlebitis 4%) when using Diazemuls, a new formulation in which diazepam is dissolved in oil and emulsified in water. Since no difference in the therapeutic effect of the different formulations was observed, Diazemuls represents a clear advantage to Stesolid and Stesolid MR.

Thrombophlebitis associated with vitamin E therapy. With a commentary on other medical side effects.

I have encountered 50 patients with clinical thrombophlebitis involving the lower extremites, with or without associated edema and pulmonary embolism, in whom longstanding self-medication with large amounts of vitamin E appeared to be a significant factor. The majority improved following cessation of vitamin E. In view of the epidemic nature of thrombophlebitis and deep vein thrombosis in the United States, the presumed innocuousness of vitamin E therapy requires reevaluation. Other clinical side effects also have been noted in patients receiving large doses of vitamin E. They include breast tenderness, elevation of blood pressure, a fatigue syndrome, myopathy, intestinal cramps, urticaria, and the possible aggravation of diabetes mellitus. The influence of concomitant metabolic, endocrine, and cardiovascular disorders on the thrombogenic potential of vitamin E is raised, and several possible mechanisms conducive to thrombophlebitis are reviewed.

First pass conjugation and enterohepatic recycling of oxazepam in dogs; intravenous tolerance of oxazepam in propylene glycol.

Oxazepam dissolved in propylene glycol was administered intravenously to dogs. There were no cardiac or general adverse effects. Hemolysis and thrombophlebitis were observed after rapid infusion (5.6 ml in 1 minute), and were shown to be due to the properties of the vehicle. Comparison of plasma concentration time curves after oral and intravenous administration indicated a bioavailability of 70 +/- 15 S.D. %. The decreased availability after oral dose was considered to be due to first pass elimination as the urinary recovery of metabolites was the same after the two routes of administration. This also indicates complete absorption. In a dog with a chronic biliary fistula 15 mg of oxazepam was given intravenously on two occasions. When normal bile flow into the gut was permitted the disposition of oxazepam was similar to that in normal dogs. When bile was withdrawn the elimination of oxazepam was more rapid with an increase of apparent plasma clearance. In this case 32% of the dose was excreted as conjugates in the bile within 3 hours after administration. In the normal dogs 2-20% of the dose given was recovered in the faeces as the parent compound and practically no conjugates were found. These findings indicate enteral hydrolysis of the conjugates, and a marked enterohepatic recycling or oxazepam.